Israel Medical Association Journal

Background: Bicalutamide monotherapy (BMT) is an option for androgen deprivation therapy (ADT) in patients with low- and intermediate-risk prostate cancer (LIR-PC). Painful gynecomastia (PG) is a common side effect of BMT. Few therapeutic options are available for preventing BMT-induced PG.

Objectives: To assess the efficacy and side effects of single fraction (SF) prophylactic breast irradiation (PBI) to prevent painful gynecomastia (PG) in patients LIR-PC treated with BMT.

Methods: We reviewed the results of bilateral PBI in a prospective cohort of LIR-PC patients who received 150 mg bicalutamide daily as a first-line treatment for at least 12 months. A single fraction of 8 Gy was administered to both breasts by a stationary field of 10 × 10 cm, using 10–15 MeV electron beam. PBI was commenced on the same day as BMT, but prior to the first dose of bicalutamide. A radiotherapy treatment plan was designed to cover breast tissue by the 90% isodose line. Subsequent monthly physical examinations were scheduled for all patients during the first year of BMT to evaluate any PG symptoms.

Results: Seventy-six patients received BMT and PBI, 80% (61/76) showed no signs of PG; 20% (15/76) experienced mild gynecomastia. The main adverse effect of PBI was grade 1 radiation dermatitis.

Conclusions: PBI using a SF of 8 Gy is an effective, safe, and low-cost strategy for the prevention of BMT-induced PG in LIR-PC patients.

Background: Prophylactic cranial irradiation (PCI) exclusion in favor of brain magnetic resonance imaging (MRI) staging and surveillance in the management of small cell lung cancer (SCLC) is controversial yet accepted by some centers. The use of MRI suggests performing stereotactic radiosurgery (SRS) treatment for limited brain metastases. Data regarding SRS efficacy in this setting is limited.

Objectives: To assess intracranial objective response rate (iORR), progression-free survival (iPFS), intracranial failure patterns, overall survival (OS) and time-to-whole-brain radiation therapy (WBRT)/death, whichever occurred first (TTWD) with SRS in SCLC.

Methods: The study comprised 10 consecutive SCLC patients with brain metastases treated with SRS and followed-up at Davidoff Cancer center between Aug 2012 and March 2019. Brain MRI images were reviewed by a neuro-radiology specialist.

Results: iORR was 57% as assessed by response assessment in neuro-oncology brain metastases. Intracranial progression developed in 8 patients. Median iPFS was 4.0 months (95% confidence interval [95%CI] 1.7–7.2). In-site, off-site and combined pattern of intracranial failure was seen in 0, 5, and 3 patients, respectively; median number of new brain lesions following SRS was 4 (range, 1–12). SRS was performed 10 additional times in 6 patients (median number of lesions irradiated per round was 1, range 1–5). WBRT was administered in 3 patients. Median TTWD was 20.9 months (95% CI, 1.9–26.8). Median OS since SRS administration was 23.2 months (95% CI, 4.2–not reached).

Conclusions: MRI surveillance with multiple rounds of SRS may serve a reasonable alternative to PCI or therapeutic WBRT in SCLC. 

Background: Patients with right bundle branch block (RBBB) prior to transcatheter aortic valve implantation (TAVI) are at high risk for immediate post-procedural heart block and long-term mortality when discharged without a pacemaker.

Objectives: To test whether prophylactic permanent pacemaker implantation (PPI) is beneficial.

Methods: Of 795 consecutive patients who underwent TAVI, 90 patients had baseline RBBB. We compared characteristics and outcomes of the prophylactic PPI with post-TAVI PPI. Need for pacing was defined as  greater than 1% ventricular pacing.

Results: Forty patients with RBBB received a prophylactic PPI (group 1), and in 50 the decision was based on standard post-procedural indications (group 2). There were no significant differences in clinical baseline characteristics. One patient developed a tamponade after a PPI post-TAVI. A trend toward shorter hospitalization duration in group 1 patients was observed (P = 0.06). On long-term follow-up of 848 ± 56 days, no differences were found in overall survival (P = 0.77), the composite event-free survival of both mortality and hospitalizations (P = 0.66), or mortality and syncope (P = 0.65). On multivariate analysis, independent predictors of the need for pacing included baseline PR interval increase of 10ms (odds ratio [OR] 1.21 per 10 ms increment 95% confidence interval [95%CI] 1.02–1.44, P = 0.028), and the use of new generation valves (OR 3.92, 95%CI 1.23–12.46, P = 0.023).

Conclusions: In patients with baseline pre-TAVI RBBB, no outcome differences were found with prophylactic PPI. On multivariate analysis, predictors of the need for pacing included baseline long PR interval, and the use of newer generation valves.

Women who carry the BRCA gene mutation have an up to 80% chance of developing cancer, primarily of breast and ovarian origin. Confirmation of carrier status is described by many women as an overwhelming, life-changing event. Healthy individuals harboring a BRCA mutation constitute a high risk population with unique needs, often overlooked by health authorities. As such, we felt the need to create a specialized service dedicated specifically to this high risk population. The clinic staff comprises an experienced multidisciplinary team of health professionals who can support the medical and emotional needs of this population. Since its inception in 2001 the clinic has served 318 women. The mean age of patients is 46 years. With a median follow-up of 46 months, 21 women have developed malignancies, including 17 breast cancers, 1 ovarian cancer and 3 additional cancers. All but one of the patients above the age of 40 underwent bilateral salpingo-oophorectomy (BSO). The median and mean ages at BSO were 46.5 and 48 years, respectively (range 33–68). However, only 28.3% underwent bilateral preventive mastectomy. A multidisciplinary clinic for BRCA mutation carriers provides a “home” for this unique population with unmet needs. The high rate of BSO in women before natural menopause indicates that both the medical community and this population are aware of international guidelines supporting this procedure. We believe that a dedicated clinic, with a multidisciplinary team, is likely to contribute to the health, quality of life and survival of BRCA carriers.

Background: Enoxaparin is frequently used as prophylaxis for deep venous thrombosis in critically ill patients. 

Objectives: To evaluate three enoxaparin prophylactic regimens in critical care patients with and without administration of a vasopressor.

Methods: Patients admitted to intensive care units (general and post-cardiothoracic surgery) without renal failure received, once daily, a subcutaneous fixed dose of 40 mg enoxaparin, a subcutaneous dose of 0.5 mg/kg enoxaparin, or an intravenous dose of 0.5 mg/kg enoxaparin. Over 5 days anti-activated factor X levels were collected before the daily administration and 4 hours after the injection.

Results: Overall, 16 patients received the subcutaneous fixed dose, 15 received the subcutaneous weight-based dosage, and 8 received the dose intravenously. Around two-fifths (38%) of the patients received vasopressors. There was no difference between anti-activated factor X levels regarding vasopressor administration. However, in all three groups the levels were outside the recommended range of 0.1 IU/ml and 0.3 IU/ml.

Conclusions: Although not influenced by vasopressor administration, the enoxaparin regimens resulted in blood activity levels outside the recommended range.

 

Background: Determining the accuracy of interferon gamma-releasing assays (IGRAs) is difficult due to the lack of a gold standard test for diagnosing latent tuberculosis (LTB). 

Objectives: To analyze the guidelines used for interpreting IGRAs in determining prophylactic treatment management for latent tuberculosis (LTB) in Israel.

Methods: We analyzed the retrospective data of 367 subjects who were referred to our laboratory during the period 2007–2011 for QuantiFERON Test-Gold In Tube (QFT-GIT) tests because of suspected LTB. Demographics and clinical data were retrieved from a questionnaire at enrollment, and 166/367 (45%) were further interviewed by phone in order to complete follow-up information on prophylactic TB treatment. 

Results: The majority of subjects (116/166, 69.9%, P < 0.0001) were spared prophylactic treatment subsequent to QFT-GIT testing. Subjects with negative QFT-GIT and positive tuberculin skin test (TST) results who were BCG-vaccinated had the lowest treatment rates (6/68, 8.8%, P < 0.0001). Most BCG-vaccinated subjects with positive TST and negative QFT-GIT test results received treatment with anti-tumor necrosis factor-alpha (TNFα) (17/19, 89.5%, P = 0.004). We found more negative QFT-GIT test results in subjects who were receiving anti-TNFα or steroid and other immunosuppressive treatment prior to testing (11/11, 100%, P = 0.029; 22/26, 84.6%, P = 0.06; 15/17, 88%, P = 0.06, respectively). 

Conclusions: Deciding on LTB prophylactic treatment in Israel is highly influenced by QFT-GIT test results. QFT-GIT findings contribute to clinical decisions, but their interpretation must also consider the patient’s medical history and clinical characteristics. 

 

Background: Although febrile urinary tract infections are very common in young children, the need for antimicrobial prophylaxis and evaluation following a first event is controversial.

Objectives: To assess the approach of leading pediatric specialists throughout Israel.

Methods: A questionnaire regarding the approach to antibiotic prophylaxis and diagnostic evaluation following a first event of febrile UTI[1], according to age and underlying renal abnormality, was sent to all 58 directors of departments of pediatrics, units of pediatric infectious diseases and pediatric nephrology in Israel.

Results: Fifty-six directors (96%) responded. Most prescribed prophylactic antibiotics after UTI. Heads of infectious disease departments prescribed less prophylaxis following UTI at the age of 18 months than heads of pediatrics or heads of pediatric nephrology units (34% vs. 72–75%, P = 0.018), but more often in cases of severe vesico-ureteral reflux without UTI. Cephalosporins were used prophylactically more often by directors of pediatrics compared to heads of pediatric nephrology units (71% vs. 38%, P = 0.048); the latter used non-beta-lactam prophylaxis (61% vs. 23%, P = 0.013) more often. Most pediatricians used renal sonography for evaluation; renal scan was used more commonly by pediatric nephrologists.

Conclusions: The administration of prophylactic antibiotics after UTI is still common practice among pediatric opinion leaders, although the specific approach differs by subspecialty. According to up-to-date evidence-based data, educational efforts are needed to formulate and implement judicious guidelines.

Background: In both adjuvant arthritis and rheumatoid arthritis edema and inflammation appear in synovial joints. Edema or effusion reflects an imbalance in lymph dynamics. Purified micronized flavonoid fraction is mainly used in the treatment of chronic venous insufficiency. This compound improves lymphatic drainage with a signicant increase in lymphatic flow and lymphatic pulsality. It is suggested that the beneficial effect of purified micronized flavonoid fraction may be involved in the treatment of adjuvant arthritis in rats.

Objectives: To evaluate the effect of Detralex on methotrexate prophylactic treatment of adjuvant arthritis in rats.

Methods: Groups of rats with adjuvant arthritis were treated with methotrexate (0.6 mg/kg/week), Detralex (20 mg/kg/day) and their combination for 50 days from adjuvant application. Hind paw swelling, arthrogram scores, serum albumin level, serum nitrite/nitrate concentrations, whole body mineral density and X-ray scans of synovial joints were evaluated as markers of inflammation and destructive changes associated with arthritis.

Results: Long-term prophylactic treatment with low dose methotrexate significantly inhibited the markers of both inflammation and arthritis. Detralex administered alone slightly decreased both the hind paw swelling and the arthritic score. Other inflammatory and arthritic markers were not significantly influenced. However, detralex combined with methotrexate markedly potentiated the beneficial effects of methotrexate, which resulted in a more significant reduction in hind paw swelling, arthritic scores, and serum concentrations of nitrite/nitrate. Interestingly, the arthritis-induced decrease of BMD[1] in AA[2] rats was significantly lower only in the group treated with the combination of Detralex+methotrexate.

Conclusion: Detralex increased the therapeutic efficacy of methotrexate basal treatment in AA. We suggest that this may be related to the beneficial effect of Detralex on microcirculation, especially on venules and lymphatic vessels.

Background: Mucositis and dermatitis are frequently encountered in patients treated with radiochemotherapy. Dead Sea products that contain minerals and different substances have proved effective in treating various skin diseases.

Objectives: To evaluate the effectiveness of Dead Sea products in reducing acute radiochemotherapy‑induced side effects in patients with head and neck cancer.

Methods: In this phase 2 study we compared the outcomes in 24 treated patients and 30 conventionally treated patients matched for age, tumor site, and type of treatment. The Dead Sea products comprised a mouthwash solution (Lenom®) and a skin cream (Solaris®) used three times daily for 1 week before, during, and up to 2 weeks after completion of radiotherapy. Mucositis and dermatitis were evaluated using common toxicity criteria.

Results: Thirteen treated patients (54%) had grade 1-2 and none had 3-4 mucositis, while 17 controls (57%) had grade 1-2 and 4 (13%) had grade 3-4 mucositis. Thirteen treated patients (54%) had grade 1-2 dermatitis; there was no instance of grade 3-4 dermatitis, while 11 patients in the control group (37%) had grade 1-2 and 5 (17%) had grade 3-4 dermatitis. More patients in the control arm needed a break than the patients in the treatment arm (P = 0.034[T1]).

Conclusions: The two Dead Sea products tested decreased skin and mucosal toxicity in head and neck cancer patients receiving radiochemotherapy.